Endocrine Regulation of Extra-skeletal Organs by Bone-derived Secreted Protein and the effect of Mechanical Stimulation

Abstract

Bone serves as the support for body and provide attachment points for the muscles. The musculoskeletal system is the basis for the human body to complete exercise. Studies believe that bone is not only the basis for constructing structures, but also participates in the regulation of organs outside bone. The realization of this function is closely related to the protein secreted by bone. Whether bone can realize their positions in the human body is also related to their secretion. Bone-derived proteins provide a medium for the targeted regulation of bones on organs, making the role of bone in human body more profound and concrete. Mechanical stimulation effects the extra-skeletal organs by causing quantitative changes in bone-derived factors. When bone receives mechanical stimulation, the nichle of bone responds, and the secretion of various factors changes. However, whether the proteins secreted by bone can interfere with disease requires more research. In this review article, we will first introduce the important reasons and significance of the in-depth study on bone-derived secretory proteins, and summarize the locations, structures and functions of these proteins. These functions will not only focus on the bone metabolism process, but also be reflected in the cross-organ regulation. We specifically explain the role of typical bone-derived secretory factors such as osteocalcin (OCN), osteopontin (OPN), sclerostin (SOST) and fibroblast growth factor 23 (FGF23) in different organs and metabolic processes, then establishing the relationship between them and diseases. Finally, we will discuss whether exercise or mechanical stimulation can have a definite effect on bone-derived secretory factors. Understanding their important role in cross-organ regulation is of great significance for the treatment of diseases, especially for the elderly people with more than one basic disease.

Keywords: bone; cross-organ regulation; endocrine regulation; exercise prescription; mechanical stimulation; secreted protein.

FIGURE 1

The effect of bone-derived factors on brain at all stages. OCN affects the development of fetal hippocampus through fetal blood, and the GPR158 receptors that acted on adults affects the synthesis of neurotransmitters. For elderly, OPN affects inflammatory plaques and promotes the remyelination and formation of AD patients. Improve the function of the blood-brain barrier in patients with acute brain injury.

FIGURE 2

The effect of bone-derived factors on modules of musculoskeletal system. FGF23 affects muscle metabolism. It is associated with cardiomyocytes through FGFR4 and acts on α-Klotho to change aortic smooth muscle. OPN affects skeletal muscles, and the increase in a certain range after injury will help recovery, but long-term increase of OPN will lead to muscle fibrosis and affect muscle function. SOST affects arthritis through the Wnt/β-catenin signaling pathway, which can inhibit the activity of enzyme inhibitor RNA, promote subchondral bone sclerosis, and inhibit cartilage degradation.

FIGURE 3

Mechanical stimulation as an influencing factor of bone-derived factors. OCN rises within 1 hour after mechanical stimulation, and through the participation of actin binding protein cofilin, it promotes ASR, memory and muscle function. Mechanical stimulation also promotes the content of OPN, the Akt1 signaling pathway can promote bone remodeling caused by mechanical stress and hypertension-related vascular remodeling. The relationship between SOST content and mechanical stimulation is that SOST rises sharply after short-term mechanical stimulation and then drops below the baseline level. Long-term stimulation slows down the increase of SOST, which has an inhibitory effect. SOST promotes bone resorption and improves the bone density and microstructure of CKD rats through the Wnt signaling pathway. FGF23 rises briefly after receiving mechanical stimulation, and then drops to the baseline level slowly. Through Klotho-FGF23 signaling pathway, the activation of bone cells is enhanced and parameters of uremia will be improved.